Adoptive immunotherapy has proven useful to treat human melanoma. The use of lymphokine activated killer cells and tumor infiltrating lymphocytes in conjunction with IL-2 have produced significant results in some terminal cancer patients. Recently, interferon alpha has been shown to have a synergistic effect with IL-2/TIL in animal TIL models. To further enhance TIL therapy, a Phase I study (Section D) involved constructing retroviral vectors to express alpha-IFN in human TIL cells. The Phase II study will optimize the expression of IFN alpha in TIL cells, and in tumor cells themselves. These vectors will be studied in rodent models, and compared with another interferon vector, IFN gamma, that has independently been constructed at GTI. It is of interest to compare these two interferons, since IFN alpha is known to up-regulate class I MHC while IFN gamma up-regulates MHC class I and II. After suitable preclinical and safety studies, a clinical protocol to treat malignant melanoma and possibly other cancer patients is proposed to be prepared by our clinical collaborators at the NIH, and after RAC and FDA approval of such physician-sponsored protocols, a clinical study will be conducted at the NIH. The GTI group will provide clinically certified retroviral vectors for this clinical study.